The 5-HT 1B and 5-HT 1D receptors appear to play a significant role in at lest four medically important processes: thermoregulation, appetite control, anxiety, and obsessive-compulsive disorders. These receptors are difficult to study due to their low density, interference by other serotonin receptor sites, and large species differences in their distribution. Furthermore, few useful drugs are currently available for studying the biology of these receptors. In an effort to better understand these potential sites for drug development, we propose to clone and characterize the 5-HT 1B and 5-HT 1D receptors from cDNA and genomic libraries. The 5-HT 1B and 5-HT 1D receptor clones will serve as probes for determining tissue levels of gene expression as well as the genomic structure of the receptor genes. Sequence analysis of these clones will be useful in determining their relations to each other, to other serotonin receptor subtypes, and to other members of the G-protein receptor superfamily. Heterologous expression of these receptors in mammalian cell lines should also help in further delineating their pharmacological properties and second messenger coupling, providing leads for the development of new therapeutic agents for appetite control, anxiety and obsessive-compulsive disorders.